Androgen regulation of corticotropin-releasing hormone receptor 2 (CRHR2) mRNA expression and receptor binding in the rat brain.
Androgen regulation of corticotropin-releasing hormone receptor 2 (CRHR2) mRNA expression and receptor binding in the rat brain.
复制标题
雄激素对大鼠脑中促肾上腺皮质激素释放激素受体 2 (CRHR2) mRNA 表达和受体结合的调节。
DOI：
10.1016/j.expneurol.2008.07.013
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发表时间：
2008
影响因子：
5.3
通讯作者：
Handa,RobertJ
中科院分区：
文献类型：
--
作者：
Weiser,MichaelJ;Goel,Nirupa;Sandau,UrsulaS;Bale,TracyL;Handa,RobertJ
压力引起的情感障碍，例如抑郁和焦虑，在女性中比男性更常见。男性对这些疾病的脆弱性降低可能是由于雄激素的存在，众所周知，雄激素可以抑制压力反应并减少焦虑样行为。然而，这种性别差异的神经生物学机制尚未阐明。促肾上腺皮质激素释放激素受体 2 (CRHR2) 与调节焦虑型行为有关，并在压力反应性大脑区域表达，该区域也含有雄激素受体 (AR)。我们假设雄激素可能通过作用于 CRHR2 发挥其作用，因此我们研究了雄激素给药后雄性大鼠前脑中 CRHR2 mRNA 和受体结合的调节。年轻成年雄性 Sprague/Dawley 大鼠被切除性腺 (GDX)，并使用激素填充的硅橡胶胶囊用不可芳香化的雄激素、丙酸二氢睾酮 (DHTP) 进行治疗。对照动物接受空胶囊。使用定量实时 RT-PCR，测定块解剖脑区域中的 CRHR2 mRNA 水平。与媒介物处理的对照相比，DHTP 处理显着增加了海马、下丘脑和侧隔膜中 CRHR2 mRNA 的表达 (p<0.01)。在杏仁核中观察到类似的趋势（p = 0.05）。此外，体外放射自显影显示，雄激素治疗的男性外侧隔膜中的 CRHR2 结合显着更高，其中腹侧外侧区域观察到的差异最高。还使用体外方法检查了 AR 对 CRHR2 mRNA 的调节。海马神经元含有高水平的 AR，从 E17-18 大鼠胎儿中收获，并在原代培养物中维持 14 天。然后用二氢睾酮（DHT；1 nM）、DHT 加氟他胺（雄激素受体拮抗剂）或载体处理神经元 48 小时。使用定量实时 RT-PCR 测量 CRHR2 mRNA 水平。与体内研究一致，与媒介物处理的对照相比，DHT 显着增加了海马神经元中 CRHR2 mRNA 的表达 (p<.02)。氟他胺治疗阻止了 DHT 对 CRHR2 mRNA 的影响，表明 DHT 对 CRHR2 表达的影响是 AR 介导的。因此，CRHR2 基因似乎是 AR 调节的目标，这些数据表明雄激素可能改变情绪和焦虑相关行为的潜在机制。
Stress-induced affective disorders, such as depression and anxiety, are more prevalent in females than in males. The reduced vulnerability to these disorders in males may be due to the presence of androgens, which are known to dampen the stress response and reduce anxiety-like behaviors. However, a neurobiological mechanism for this sex difference has yet to be elucidated. Corticotropin-releasing hormone receptor 2 (CRHR2) has been implicated in regulating anxiety-type behaviors and is expressed in stress-responsive brain regions that also contain androgen receptors (AR). We hypothesized that androgen may exert its effects through actions on CRHR2 and we therefore examined the regulation of CRHR2 mRNA and receptor binding in the male rat forebrain following androgen administration. Young adult male Sprague/Dawley rats were gonadectomized (GDX) and treated with the non-aromatizable androgen, dihydrotestosterone propionate (DHTP) using hormone filled Silastic capsules. Control animals received empty capsules. Using quantitative real-time RT-PCR, CRHR2 mRNA levels were determined in block-dissected brain regions. DHTP treatment significantly increased CRHR2 mRNA expression in the hippocampus, hypothalamus, and lateral septum (p<0.01) when compared to vehicle-treated controls. A similar trend was observed in amygdala (p= 0.05). Furthermore, in vitro autoradiography revealed significantly higher CRHR2 binding in the lateral septum in androgen-treated males, with the highest difference observed in the ventral lateral region. Regulation of CRHR2 mRNA by AR was also examined using an in vitro approach. Hippocampal neurons, which contain high levels of AR, were harvested from E17–18 rat fetuses, and maintained in primary culture for 14 days. Neurons were then treated with dihydrotestosterone (DHT; 1 nM), DHT plus flutamide (an androgen receptor antagonist), or vehicle for 48 h. CRHR2 mRNA levels were measured using quantitative real-time RT-PCR. Consistent with in vivo studies, DHT significantly increased CRHR2 mRNA expression in hippocampal neurons (p<.02) compared to vehicle-treated controls. Flutamide treatment prevented the effect of DHT on CRHR2 mRNA indicating that DHT's effect on CRHR2 expression is AR-mediated. Thus, the CRHR2 gene appears to be a target for regulation by AR and these data suggest a potential mechanism by which androgen may alter mood and anxiety-related behaviors.